My major objective is to understand transcriptional regulation in higher cells. To meet this objective, two areas of study are being carried out. The primary area of study will deal with transcription in Drosophila. The large and complex genome of higher cells can be simplified by isolating unique DNA fragments. This is now being accomplished by biochemically iserting EcoRI restriction endonuclease cleaved Drosophila DNA into the center of bacteriophage lambda DNA. These lambda-Drosophila hybrid DNA molecules yield viable plaque forming phage that can be easily propagated in E. coli cells. We presently have isolated about 10 to the 3rd power lambda-Drosophila transducing phages by these means. Utilizing this new technology we plan to develop methods for isolating any specific genome segment that corresponds to a known function in the organism. In particular, we must be able to isolate either whole chromomeric units or a set of tandem segments that equal a whole chromomer. If we can accomplish this, we will be ideally set up for studying the transcription patterns and controls in Drosophila. We want to define the chromomeric unit at the molecular level, the total transcription unit, and that fraction of the total transcription unit that corresponds to the mRNA and that codes for a protein. Great progress has been made on developing the technology for physically mapping point mutations. Therefore, by isolating lambda- Drosophila hybrids carrying a mutant fragment, a correlation can be made between the transcription maps just described and the genetic map. The second area of study will deal with transcription in E. coli cells. We are presently concentrating on the mechanism of termination of transcription. The N gene product and possible Q gene product appear to cause antitermination. We hope to test this in vitro.